Globally, major birth defects impact the morbidity and mortality of millions of children annually. Estimates suggest that only about one-third of defects that occur can be attributed to known environmental (broadly defined) or genetic factors. To advance the knowledge of risk factors associated with major birth defects, this application proposes to extend and expand the Iowa Center for Birth Defects Research and Prevention (IA_CBDRP) at The University of Iowa (UI). The IA_CBDRP is a collaborative effort between the Iowa Registry for Congenital and Inherited Disorders (IRCID) and investigators in the UI Colleges of Public Health, Medicine, and Pharmacy. For over 25 years, the IRCID has been a model birth defects surveillance system, and for over 20 years, UI investigators have made substantial contributions to birth defects epidemiology in areas ranging from methods development to identification of gene-environment interaction effects for specific defects. In addition, Iowa is well-suited as a sentinel state to examine risks associated with rural exposures and residences that might adversely impact fetal development, particularly pesticides, nitrates in drinking water, and emerging zoonotic infections. Exploration of these risk factors will have important public health significance not only for Iowans, but also nationally. For the proposed application, the overall goals of the IA_CBDRP will be to: 1) support the continuance and expansion of epidemiologic research capability through participation in the National Birth Defects Prevention Study (NBDPS) and 2) utilize, implement, and evaluate birth defects surveillance data for studies of environmental exposures, genetic factors, and their potential interaction effects. To accomplish these goals, the IA_CBDRP proposes to: 1) conduct ongoing data collection activities for the NBDPS, including subject ascertainment, maternal telephone interviews, and buccal sample collection; 2) build on pilot tested approaches to evaluate surveillance methodology and current DNA collection methods and also explore alternative methods of sample collection; 3) continue to evaluate follow-up questionnaires for selected exposures through local research studies with CBDRP investigators that can be expanded to all CBDRPs; and 4) expand analysis of local and pooled data to generate scientific presentations and publications and disseminate surveillance data in local and national reports. In implementing these aims, the IA_CBDRP proposes to continue its leadership role in examining behavioral, environmental, occupational, and genetic factors, expand its role in investigations of medications, infections, and nutritional factors, and continue its leadership role in methodologic studies. The expertise in the IA_CBDRP along with available UI and State of Iowa infrastructure will permit comprehensive examination of risks associated with prevalent environmental exposures, the contribution of genetic variation to such risks, as well as to examine potential, emerging risk factors for major birth defects. Findings generated will be used for family education, improvements in treatment, and application of prevention strategies.